High Dose Ascorbic Acid Treatment of CMT1A

• ClinicalTrials.gov Identifier: NCT00484510
• Recruitment Status: Completed
• First Posted: June 11, 2007
• Last Update Posted: March 6, 2013
• Sponsor: Wayne State University
• Collaborators: Muscular Dystrophy Association; Charcot-Marie-Tooth Association
• Information provided by (Responsible Party): Michael E. Shy, MD, Wayne State University

Study Description

Brief Summary:

This study will look at the impact of ascorbic acid (Vitamin C) on the progression of disease in people with CMT1A as compared to volunteers receiving a placebo. This study will assess whether is it futile to proceed with a larger, longer-term, placebo-controlled study.

Condition or disease	Intervention/treatment	Phase
Charcot-Marie-Tooth Disease, Type Ia	Drug: Ascorbic acid (Vitamin C); Drug: placebo	Phase 2; Phase 3

Detailed Description:

Charcot Marie Tooth disease (CMT), or inherited peripheral neuropathies, are among the most frequent heritable disorders, affecting approximately 1 in 2500 people. The most frequent genetic form of CMT is CMT1A. CMT1A is caused by a 1.4 Mb duplication within chromosome 17p11.2 in the region containing the PMP22 gene. Most subjects with CMT1A have a "typical" phenotype characterized by onset in childhood or early adulthood, distal weakness, sensory loss, foot deformities and absent reflexes. How increased expression of PMP22 causes these disabilities is unknown but is currently being investigated in both animal and tissue culture systems. In this study, researchers will evaluate whether ascorbic acid (Vitamin C), administered orally, slows clinical progression of CMT1A and affects the PMP22 mRNA levels of myelinated peripheral nerve fibers obtained from biopsies of glabrous skin.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-controlled, Double Masked 120 Subject "Futility Design" Clinical Trial of Ascorbic Acid Treatment of Charcot Marie Tooth Disease Type 1A.
• Study Start Date: April 2007
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ascorbic Acid	Drug: Ascorbic acid (Vitamin C); Eight 500 mg capsules/day of ascorbic acid. Subjects will take four (4)capsules each morning and four (4) capsules each evening for 24 months. (Total 4 gr/day).
Placebo Comparator: Placebo	Drug: placebo; Eight 500 mg capsules/day of placebo. Subjects will take four (4)capsules each morning and four (4) capsules each evening for 24 months.

Outcome Measures

Primary Outcome Measures :

1. Mean change in the CMT Neuropathy Scale following high dose ascorbic acid ingestion, assessed at baseline and every 6 months throughout the trial. [ Time Frame: 25 months per subject from baseline to completion. ]

Secondary Outcome Measures :

1. Evaluation of PMP22 mRNA levels of myelinated peripheral nerve fibers. [ Time Frame: Baseline and Month 24. ]

Eligibility Criteria

• Ages Eligible for Study: 13 Years to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• The subject has CMT1A, defined by the duplication on chromosome 17p11.2 performed by either Pulse Field Gel Electrophoresis or Fluorescence In Situ Hybridization (FISH) by a CLIA certified laboratory, OR the subject has a first or second degree relative with a documented duplication performed by the above methods AND the subject has uniform motor conduction slowing of the median or ulnar nerve between 16 and 30 m/s.
• The subject is between 13 and 70 years of age.
• The subject, if 18 years or older, has signed the Informed Consent Form and agrees to follow the stipulations of the protocol.
• If the subject is less than 18, his or her parents or guardians have signed the Informed Consent Form and agree to follow the stipulations of the protocol. The subject has also signed a written assent form.

Exclusion Criteria:

• A known neuropathy from another source (For example, diabetes, drug induced, alcohol, etc.)
• The subject has ever received Vincristine.
• The subject has a known allergy to ascorbic acid.
• The subject has ever had kidney stones.
• The subject has a known history of G6PD deficit.
• The subject has a history of hemochromatosis.
• The subject suffers from a serious illness or medical condition that is not stabilized or that could require hospitalization.
• The subject has a high ascorbic acid level at screening.
• The subject is pregnant or nursing.
• The subject, in the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any other reason.
• The subject participates to another clinical trial or is still within a washout period of a previous clinical trial.
• The subject is taking neurotoxic medications.

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins University, Dept of Neurology

Baltimore, Maryland, United States, 21287

United States, Michigan

Wayne State University, Dept of Neurology

Detroit, Michigan, United States, 48201

United States, New York

University of Rochester Medical Center, Dept of Neurology

Rochester, New York, United States, 14642

Sponsors and Collaborators

Wayne State University

Muscular Dystrophy Association

Charcot-Marie-Tooth Association

Investigators

• Principal Investigator: Richard A Lewis, MD; Wayne State University, Dept. of Neurology

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lewis RA, McDermott MP, Herrmann DN, Hoke A, Clawson LL, Siskind C, Feely SM, Miller LJ, Barohn RJ, Smith P, Luebbe E, Wu X, Shy ME; Muscle Study Group. High-dosage ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A: results of a randomized, double-masked, controlled trial. JAMA Neurol. 2013 Aug;70(8):981-7. doi: 10.1001/jamaneurol.2013.3178.

• Responsible Party: Michael E. Shy, MD, Professor, Wayne State University
• ClinicalTrials.gov Identifier: NCT00484510
• Other Study ID Numbers: HIC074406MP2F; MDA4193
• First Posted: June 11, 2007
• Last Update Posted: March 6, 2013
• Last Verified: March 2013

Keywords provided by Michael E. Shy, MD, Wayne State University:

Ascorbic Acid; Vitamin C; Charcot Marie Tooth; CMT; CMT1a

Additional relevant MeSH terms:

Tooth Diseases; Charcot-Marie-Tooth Disease; Nerve Compression Syndromes; Hereditary Sensory and Motor Neuropathy; Stomatognathic Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Ascorbic Acid; Vitamins; Micronutrients; Physiological Effects of Drugs; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents